NMR Determination of Oligonucleotide Structure

Thomas L. James1

1 University of California, San Francisco, California
Publication Name:  Current Protocols in Nucleic Acid Chemistry
Unit Number:  Unit 7.2
DOI:  10.1002/0471142700.nc0702s00
Online Posting Date:  May, 2001
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Abstract

This unit provides an overview of the use of NMR to determine oligonucleotide structure. It covers basic NMR spectral properties, acquisition of interproton distance restraints and torsion angle restraints, structure refinement, assessment of the quality of the structure obtained. Software programs used in the process are also described.

     
 
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Table of Contents

  • Overview of Oligonucleotide Structure Determination by NMR
  • Basic NMR Spectral Parameters
  • Acquisition of Interproton Distance Restraints
  • Aquisition of Torsion‐Angle Restraints
  • Structure Refinement
  • Assessment of Structure Quality
  • Analysis of Nucleic Acid Structure
  • Acknowledgments
  • Literature Cited
  • Figures
  • Tables
     
 
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Materials

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Literature Cited

Literature Cited
   Abragam, A. 1961. Principles of Nuclear Magnetism. Oxford University Press, Oxford.
   Adams, B. and Lerner, L. 1992. A simple one‐dimensional method for measuring proton exchange rates in water. J. Magn. Reson. 96:604‐607.
   Altona, C. and Sundaralingam, M. 1972. Conformational analysis of the sugar ring in nucleosides and nucleotides. A new description using the concept of pseudorotation. J. Am. Chem. Soc. 94:8205‐8212.
   Boelens, R., Koning, T.M.G., van der Marel, G.A., van Boom, J.H., and Kaptein, R. 1989. Iterative procedure for structure determination from proton‐proton NOEs using a full relaxation matrix approach. Application to a DNA octamer. J. Magn. Reson. 82:290‐308.
   Borgias, B.A. and James, T.L. 1989. Two‐dimensional nuclear Overhauser effect: Complete relaxation matrix analysis. Methods Enzymol. 176:169‐183.
   Borgias, B.A. and James, T.L. 1990. MARDIGRAS—Procedure for matrix analysis of relaxation for discerning geometry of an aqueous structure. J. Magn. Reson. 87:475‐487.
   Brünger, A. and Nilges, M. 1993. Computational challenges for macromolecular structure determination by X‐ray crystallography and solution NMR‐spectroscopy. Q. Rev. Biophys. 26:49‐125.
   Cavanagh, J., Fairbrother, W.J., Palmer, A.G., III, and Skelton, N.J. 1996. Protein NMR Spectroscopy: Principles and Practice. Academic Press, San Diego.
   Celda, B., Widmer, H., Leupin, W., Chazin, W.J., Denny, W.A., and Wüfthrich, K. 1989. Conformational studies of d‐(AAAAATTTTT)2 using constraints from nuclear Overhauser effects and from quantitative analysis of the cross‐peak fine structures in two‐dimensional 1H nuclear magnetic resonance spectra. Biochemistry 28:1462‐1470.
   Conte, M.R., Bauer, C.J., and Lane, A.N. 1996. Determination of sugar conformations by NMR in larger DNA duplexes using both dipolar and scalar data: Application to d(CATGTGACGTCACATG)2. J. Biomol. NMR 7:190‐206.
   Derome, A. 1987. Modern NMR Techniques for Chemistry Research. Pergamon Press, Oxford.
   Dickerson, R.E., Bansal, M., Calladine, C.R., Diekmann, S., Hunter, W.N., Kennard, O., Lavery, R., Nelson, H.J.C., Olson, W.K., Saenger, W., Shakked, Z., Sklenar, H., Soumpasis, D.M., von Kitzing, E., Wang, A. H.‐J., and Zhurkin, V.B. 1989. Definitions and nomenclature of nucleic acid structure parameters. EMBO J. 8:1‐4.
   Ernst, R.R., Bodenhausen, G., and Wokaun, A. 1987. Principles of Nuclear Magnetic Resonance in One and Two Dimensions. Clarendon Press, Oxford.
   Gonzàlez, C., Stec, W., Kobylanska, A., Hogrefe, R., Reynolds, M., and James, T.L. 1994. Structural study of a DNA‐RNA hybrid duplex with a chiral phosphorothioate moiety by NMR: Extraction of distance and torsion angle constraints and imino proton exchange rates. Biochemistry 33:11062‐11072.
   Harbison, G.S. 1993. Interference between J‐couplings and cross‐relaxation in solution NMR spectroscopy: Consequences for macromolecular structure determination. J. Am. Chem. Soc. 115:3026‐3027.
   James, T.L. 1994. Assessment of the quality of derived macromolecular structures. Methods Enzymol. 239:416‐439.
   James, T.L. (ed.). 1995. Nuclear Magnetic Resonance and Nucleic Acids. Methods in Enzymology, Vol. 261. Academic Press, New York.
   Keepers, J.W. and James, T.L. 1984. A theoretical study of distance determinations from NMR. Two‐dimensional nuclear Overhauser effect spectra. J. Magn. Reson. 57:404‐426.
   Landy, S.B. and Rao, B.D.N. 1989. Dynamical NOE in multiple‐spin systems undergoing chemical exchange. J. Magn. Reson. 81:371‐377.
   Lane, A. N. 1995. Determination of fast dynamics of nucleic acids by NMR. Methods Enzymol. 261:413‐35.
   Lavery, R. and Sklenar, H. 1989. Defining the structure of irregular nucleic acids: Conventions and principles. J. Biomol. Struct. Dyn. 6:655‐667.
   Lavery, R. and Sklenar, H. 1996. CURVES 5.1 Helical Analysis of Irregular Nucleic Acids. Laboratoire de Biochimie Theoretique, Centre National de la Recherche Scientifique, Paris.
   Leroy, J.L., Gehring, K., Kettani, A., and Guéron, M. 1993. Acid multimers of oligodeoxycytidine strands: Stoichiometry, base‐pair characterization, and proton exchange properties. Biochemistry 32:6019‐6031.
   Liu, H., Thomas, P.D., and James, T.L. 1992. Averaging of cross‐relaxation rates and distances for methyl, methylene and aromatic ring protons due to motion or overlap: Extraction of accurate distances iteratively via relaxation matrix analysis of 2D NOE spectra. J. Magn. Reson. 98:163‐175.
   Liu, H., Kumar, A., Weisz, K., Schmitz, U., Bishop, K.D., and James, T.L. 1993. Extracting accurate distances and bounds from 2D NOE exchangeable proton peaks. J. Am. Chem. Soc. 115:1590‐1591.
   Liu, H., Spielmann, H.P., Ulyanov, N.B., Wemmer, D.E., and James, T.L. 1995. Interproton distance bounds from 2D‐NOE intensities: Effect of experimental noise and peak integration errors. J. Biomol. NMR 6:390‐402.
   Liu, H., Tonelli, M., and James, T.L. 1996. Correcting NOESY cross‐peak intensities for partial relaxation effects enabling accurate distance determination. J. Magn. Reson. B 111:85‐89.
   Macura, S. and Ernst, R.R. 1980. Elucidation of cross relaxation in liquids by 2D NMR spectroscopy. Mol. Phys. 41:95‐117.
   Marion, D. and Bax, A. 1988. P.COSY, a sensitive alternative for double‐quantum‐filtered COSY. J. Magn. Reson. 80:528‐533.
   Mujeeb, A., Clever, J.L., Billeci, T.M., James, T.L., and Parslow, T.G. 1998. Structure of the dimer initiation complex of the HIV‐1 genomic RNA. Nature Struct. Biol. 5:432‐436.
   Piantini, U., Sϕrensen, O.W., and Ernst, R.R. 1982. Multiple quantum filters for elucidating NMR coupling networks. J. Am. Chem. Soc. 104:6800‐6801.
   Post, C.B., Meadows, R.P., and Gorenstein, D.G. 1990. On the evaluation of interproton distances for three‐dimensional structure determination by NMR using a relaxation rate matrix analysis. J. Am. Chem. Soc. 112:6796‐6803.
   Ravishanker, G., Swaminathan, S., Beveridge, D.L., Lavery, R., and Sklenar, H. 1989. Conformational and helicoidal analysis of 30 ps of molecular dynamics on the d(CGCGAATTCGCG) double helix: “Curves,” dials and windows. J. Biomol. Struct. Dyn. 6:669‐699.
   Rinkel, L.J. and Altona, C. 1987. Conformational analysis of the deoxyribofuranose ring in DNA by means of sums of proton‐proton coupling constants: A graphical analysis. J. Biomol. Struct. Dyn. 4:621‐649.
   Schmitz, U. and James, T.L. 1995. How to generate accurate solution structures of double‐helical nucleic acid fragments using nuclear magnetic resonance and restrained molecular dynamics. Methods Enzymol. 261:3‐44.
   Schmitz, U., Zon, G., and James, T.L. 1990. Deoxyribose conformation. In [d(GTATATAC)]2: Evaluation of sugar pucker by simulation of double‐quantum‐filtered COSY cross‐peaks. Biochemistry 29:2357‐2368.
   Shriver, J. and Edmondson, S. 1993. Defining the precision with which a protein structure is determined by NMR. Application to motilin. Biochemistry 32:1610‐1617.
   Thomas, P.D., Basus, V.J., and James, T.L. 1991. Protein solution structure determination using distances from 2D NOE experiments: Effect of approximations on the accuracy of derived structures. Proc. Natl. Acad. Sci. U.S.A. 88:1237‐1241.
   Tonelli, M. and James, T.L. 1998. Insights into the dynamic nature of DNA duplex structure via analysis of nuclear Overhauser effect intensities. Biochemistry 37:11478‐11487.
   Tonelli, M., Ragg, E., Bianucci, A.M., Lesiak, K., and James, T.L. 1998. NMR structure of d(GCATATGATAG).d(CTATCATATGC): A consensus sequence for promoters recognized by σK RNA polymerase. Biochemistry 37:11745‐11761.
   Ulyanov, N.B. and James, T.L. 1995. Statistical analysis of DNA duplex structural features. In Nuclear Magnetic Resonance and Nucleic Acids, Vol. 261 (T.L. James, ed.) pp. 3‐44. Academic Press, New York.
   Ulyanov, N.B., Schmitz, U., and James, T.L. 1993. Metropolis Monte Carlo calculations of DNA structure using internal coordinates and NMR distance restraints: An alternative method for generating high‐resolution solution structure. J. Biomol. NMR 3:547‐568.
   Ulyanov, N.B., Schmitz, U., Kumar, A., and James, T.L. 1995. Probability assessment of conformational ensembles: Sugar repuckering in a DNA duplex in solution. Biophys. J. 68:13‐24.
   van de Ven, F.J.M. and Hilbers, C.W. 1988. Resonance assignments of non‐exchangeable protons in B type DNA oligomers, an overview. Nucl. Acids Res. 16:5713‐5726.
   Weisz, K., Shafer, R.H., Egan, W., and James, T.L. 1994. Solution structure of the octamer motif in immunoglobulin genes via restrained molecular dynamics calculations. Biochemistry 33:354‐366.
   Widmer, H. and Wüthrich, K. 1987. Simulated two‐dimensional NMR cross‐peak fine structures for 1H spin systems in polypeptides and polydeoxynucleotides. J. Magn. Reson. 74:316‐336.
   Wijmenga, S.S., Mooren, M.M.W., and Hilbers, C.W. 1993. NMR of nucleic acids; from spectrum to structure. In NMR in Macromolecules (G.C. Roberts, ed.) pp. 217‐288. IRL Press, Oxford.
   Zhu, L., Reid, B.R., and Drobny, G.P. 1995. Errors in measuring and interpreting values of coupling constants J from PE.COSY experiments. J. Magn. Reson. A 115:206‐212.
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